Early volumetric, perfusion, and diffusion MRI changes after mutant isocitrate dehydrogenase (IDH) inhibitor treatment in IDH1-mutant gliomas

Inhibition of the isocitrate dehydrogenase (IDH)-mutant enzyme is a novel therapeutic target in IDH-mutant gliomas. Imaging biomarkers of IDH inhibitor treatment efficacy in human IDH-mutant gliomas are largely unknown. This study investigated early volumetric, perfusion, and diffusion MRI changes i...

Full description

Saved in:
Bibliographic Details
Published in:Neuro-oncology advances 2022-01, Vol.4 (1), p.vdac124-vdac124
Main Authors: Cho, Nicholas S, Hagiwara, Akifumi, Eldred, Blaine S C, Raymond, Catalina, Wang, Chencai, Sanvito, Francesco, Lai, Albert, Nghiemphu, Phioanh, Salamon, Noriko, Steelman, Lori, Hassan, Islam, Cloughesy, Timothy F, Ellingson, Benjamin M
Format: Article
Language:English
Subjects:
Clinical Investigations
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Inhibition of the isocitrate dehydrogenase (IDH)-mutant enzyme is a novel therapeutic target in IDH-mutant gliomas. Imaging biomarkers of IDH inhibitor treatment efficacy in human IDH-mutant gliomas are largely unknown. This study investigated early volumetric, perfusion, and diffusion MRI changes in IDH1-mutant gliomas during IDH inhibitor treatment. Twenty-nine IDH1-mutant glioma patients who received IDH inhibitor and obtained anatomical, perfusion, and diffusion MRI pretreatment at 3-6 weeks (  = 23) and/or 2-4 months (  = 14) of treatment were retrospectively studied. Normalized relative cerebral blood volume (nrCBV), apparent diffusion coefficient (ADC), and fluid-attenuated inversion recovery (FLAIR) hyperintensity volume were analyzed. After 3-6 weeks of treatment, nrCBV was significantly increased (  = .004; mean %change = 24.15%) but not FLAIR volume (  = .23; mean %change = 11.05%) or ADC (  = .52; mean %change = -1.77%). Associations between shorter progression-free survival (PFS) with posttreatment nrCBV > 1.55 (  = .05; median PFS, 240 vs 55 days) and increased FLAIR volume > 4 cm (  = .06; 227 vs 29 days) trended toward significance. After 2-4 months, nrCBV, FLAIR volume, and ADC were not significantly different from baseline, but an nrCBV increase > 0% (  = .002; 1121 vs 257 days), posttreatment nrCBV > 1.8 (  = .01; 1121 vs. 270 days), posttreatment ADC  0% (  = .02; 1121 vs 270 days), and FLAIR volume change > 4 cm (  = .03; 421 vs 226.5 days) were associated with shorter PFS. Increased nrCBV at 3-6 weeks of treatment may reflect transient therapeutic and/or tumor growth changes, whereas nrCBV, ADC, and FLAIR volume changes occurring at 2-4 months of treatment may more accurately reflect antitumor response to IDH inhibition.
ISSN:2632-2498
2632-2498
DOI:10.1093/noajnl/vdac124